Safety and efficacy of the 5-lipoxygenase-activating protein inhibitor AZD5718 in patients with recent myocardial infarction: The phase 2a FLAVOUR study.
5-Lipoxygenase activating protein
Cardiovascular disease
Leukotriene
Randomized clinical trial
Journal
International journal of cardiology
ISSN: 1874-1754
Titre abrégé: Int J Cardiol
Pays: Netherlands
ID NLM: 8200291
Informations de publication
Date de publication:
15 10 2022
15 10 2022
Historique:
received:
21
06
2022
accepted:
12
07
2022
pubmed:
17
7
2022
medline:
30
8
2022
entrez:
16
7
2022
Statut:
ppublish
Résumé
Leukotrienes are pro-inflammatory vasoactive lipid mediators implicated in the pathophysiology of atherosclerotic cardiovascular disease. We studied the effect of the 5-lipoxygenase-activating protein inhibitor AZD5718 on leukotriene biosynthesis and coronary microvascular function in a single-blind, phase 2a study. Patients 7-28 days after myocardial infarction (±ST elevation), with <50% left anterior descending coronary artery stenosis and Thrombolysis in Myocardial Infarction flow grade ≥ 2 after percutaneous coronary intervention, were randomized 2:1:2 to once-daily AZD5718 200 mg or 50 mg, or placebo, in 4- and 12-week cohorts. Change in urine leukotriene E Of 129 randomized patients, 128 received treatment (200 mg, n = 52; 50 mg, n = 25; placebo, n = 51). Statistically significant reductions in uLTE In patients with recent myocardial infarction, AZD5718 was well tolerated, and leukotriene biosynthesis was dose-dependently inhibited. No significant changes in CFVR were detected. gov identifier: NCT03317002.
Sections du résumé
BACKGROUND
Leukotrienes are pro-inflammatory vasoactive lipid mediators implicated in the pathophysiology of atherosclerotic cardiovascular disease. We studied the effect of the 5-lipoxygenase-activating protein inhibitor AZD5718 on leukotriene biosynthesis and coronary microvascular function in a single-blind, phase 2a study.
METHODS
Patients 7-28 days after myocardial infarction (±ST elevation), with <50% left anterior descending coronary artery stenosis and Thrombolysis in Myocardial Infarction flow grade ≥ 2 after percutaneous coronary intervention, were randomized 2:1:2 to once-daily AZD5718 200 mg or 50 mg, or placebo, in 4- and 12-week cohorts. Change in urine leukotriene E
RESULTS
Of 129 randomized patients, 128 received treatment (200 mg, n = 52; 50 mg, n = 25; placebo, n = 51). Statistically significant reductions in uLTE
CONCLUSIONS
In patients with recent myocardial infarction, AZD5718 was well tolerated, and leukotriene biosynthesis was dose-dependently inhibited. No significant changes in CFVR were detected.
CLINICALTRIALS
gov identifier: NCT03317002.
Identifiants
pubmed: 35842004
pii: S0167-5273(22)01084-1
doi: 10.1016/j.ijcard.2022.07.016
pii:
doi:
Substances chimiques
5-Lipoxygenase-Activating Protein Inhibitors
0
AZD5718
0
Pyrazoles
0
Banques de données
ClinicalTrials.gov
['NCT03317002']
Types de publication
Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
34-40Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.